Michael Jewett Engineering cell-free systems for medicine, biotechnology, & synthetic biology

Research Interests

Our research group is motivated by a desire to understand, harness, and expand the capabilities of biological systems for compelling applications in medicine, materials, and energy. Specifically, we focus on designing, constructing, and modifying biological systems involved in protein synthesis and metabolism to (i) understand why nature’s designs work the way they do and (ii) open the way to products that have been impractical, if not impossible, to produce by other means. An innovative feature of our research program is the use of cell-free systems. The foundational principle is that we can conduct precise, complex biomolecular transformations without using intact cells, which provides an unprecedented and otherwise unattainable freedom of design to modify and control biological systems. For example, cell-free systems avoid the need to balance the tug-of-war that exists between the cell’s physiological and evolutionary objectives and the engineer’s process objectives. We are also pioneering new directions to repurpose the translation apparatus for synthetic biology. The goal is to monitor, interrogate, and understand the process of translation, and with this knowledge diversify, evolve and repurpose the ribosome and its peripheral machinery into a re-engineered machine to generate non-natural polymers as new classes of sequence-defined, evolvable matter. 

Our research activities are structured into four thrust areas: (1) cell-free protein synthesis and orthogonal translation systems, (2) engineered ribosomes, (3) metabolic engineering, and (4) glycosylation. These research areas are connected by approach (e.g., cell-free systems) and their focus on biocatalytic systems (e.g., the translation apparatus). They advance new understanding of biological knowledge and develop enabling technologies for the production of therapeutics, biomaterials, and biochemicals. 

Selected Publications

Single-pot glycoprotein biosynthesis using a cell-free transcription-translation system enriched with glycosylation machinery. Jaroentomeechai T, Stark JC, Natarajan A, Glasscock CJ, Yates LE, Hsu KJ, Mrksich M, Jewett MC, and DeLisa MP. Nature Communications. 2018 July 12;9:2686.

Design of glycosylation sites by rapid synthesis and analysis of glycosyltransferases. Kightlinger W, Lin L, Rosztoczy M, Li W, DeLisa MP, Mrksich M, and Jewett MC. Nature Chemical Biology. 2018 June;14(6):627-635.

Cell-free protein synthesis from genomically recoded bacteria enables multisite incorporation of noncanonical amino acids. Martin RW, Des Soye BJ, Kwon Y-C, Kay J, Davis RG, Thomas PM, Majewski NI, Chen CX, Marcum RD, Weiss MG, Stoddart AE, Amiram M, Ranji Charna AK, Patel JR, Isaacs FJ, Kelleher NL, Hong SH, and Jewett MC. Nature Communications. 2018 March 23;9:1203.

A cell-free framework for rapid biosynthetic pathway prototyping and enzyme discovery. Karim AS and Jewett MC. Metabolic Engineering. 2016 July;36:116-126.

Protein synthesis by ribosomes with tethered subunits. Orelle C, Carlson ED, Szal T, Florin T, Jewett MC, and Mankin AS. Nature. 2015 August 6;524(7563):119-124.

View all publications by Michael C. Jewett listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.